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Introduction: Many of the first line medications for the treatment of active and latent M. tuberculosis are hepatoxic and cause a spectrum of anti-tuberculosis drug induced liver injury (ATLI), including acute liver failure (ALF). Despite advances in recognition of and prevention of ATLI, isoniazid remains one of the leading causes of DILI as well as drug-induced ALF. Areas covered: A literature search of the incidence, risk factors, current societal guidelines, monitoring, and prophylactic medication usage in ATLI was performed using PubMed and institutional websites. Relevant articles from 1972 to 2024 were included in this review. Expert opinion: Current societal guidelines regarding ATLI monitoring are mixed, but many recommend liver enzyme testing of high-risk populations. We recommend liver test monitoring for all patients on multi-drug therapy as well as those on isoniazid therapy. Precision medicine practices, such as N-acetyltransferase-2 polymorphism genotyping, are thought to be beneficial in reducing the incidence of ATLI in high-risk populations. However, broader implementation is currently cost prohibitive. Hepatoprotective drugs are not currently recommended, although we do recognize their potential. In patients who develop ATLI but require ongoing anti-TB treatment, strategies to restart the same or less hepatotoxic regimens are currently being followed. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance has emerged as a global public health threat, and development of novel therapeutics for treating infections caused by multi-drug resistant bacteria is urgent. Staphylococcus aureus is a major human and animal pathogen, responsible for high levels of morbidity and mortality worldwide. The intracellular survival of S. aureus in macrophages contributes to immune evasion, dissemination, and resilience to antibiotic treatment. Here, we present a confocal fluorescence imaging assay for monitoring macrophage infection by green fluorescent protein (GFP)-tagged S. aureus as a front-line tool to identify antibiotic leads. The assay was employed in combination with nanoscaled chemical analyses to facilitate the discovery of a new, active rifamycin analogue. Our findings indicate a promising new approach for the identification of antimicrobial compounds with macrophage intracellular activity. The antibiotic identified here may represent a useful addition to our armory in tackling the silent pandemic of antimicrobial resistance.

Background Real-world experience with combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor–containing antiretroviral therapy (ART) in management of latent tuberculous infection (LTBI) is limited among people with human immunodeficiency virus (PWH). Methods From August 2019 to October 2022, PWH receiving 3 months of weekly rifapentine plus isoniazid (3HP) or 1 month of daily rifapentine plus isoniazid (1HP) in combination with ART were included. The primary outcome was virologic response within 12 months after LTBI treatment; secondary outcomes included treatment completion rate and safety of LTBI regimens. Results During the study period, 479 PWH (94.6% male; median age, 43 years) were included: 142 received 1HP and bictegravir (BIC)-containing regimens (1HP/BIC group), 46 1HP and dolutegravir (DTG)-containing regimens (1HP/DTG group), 38 3HP and BIC-containing regimens (3HP/BIC group), 214 3HP and DTG-containing regimens (3HP/DTG group), 17 1HP and other ART regimens (1HP/others group), and 22 3HP/other ART regimens (3HP/others group). In the intention-to-treat analysis, the proportions of PWH maintaining plasma HIV-1 RNA <200 copies/mL within 12 months after LTBI treatment completion were 96.5% (1HP/BIC), 100% (1HP/DTG), 100% (3HP/BIC), 95.8% (3HP/DTG), 100% (1HP/others), and 100% (3HP/others). The overall completion rates were >80% for all treatment groups, whereas >50% of the included PWH experienced any adverse event. LTBI regimens and ART combinations were not associated with virologic response and completion rate. Conclusions Combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor-containing ART maintained viral suppression for most PWH within 12 months of LTBI treatment completion with low rates of grade 3 or higher adverse events. [ABSTRACT FROM AUTHOR]

Rifamycin and its derivatives are natural products that belong to the class of antibiotic-active polyketides and have significant therapeutic relevance within the therapy scheme of tuberculosis, a worldwide infectious disease caused by Mycobacterium tuberculosis. Improving the oral bioavailability of rifamycin B was achieved through semisynthetic modifications, leading to clinically effective derivatives such as rifampicin. Genetic manipulation of the rifamycin polyketide synthase gene cluster responsible for the production of rifamycin B in the Amycolatopsis mediterranei strain S699 represents a promising tool to generate new rifamycins. These new rifamycins have the potential to be further derivatized into new, ideally more effective, clinically usable compounds. However, the resulting genetically engineered strains only produce these new derivatives in low yields. One example is the strain DCO36, in which rifAT6 was replaced by rapAT2, resulting in the production of rifamycin B and the new derivative 24-desmethyl rifamycin B. Here we describe the successful method adaptation of the PCR-targeting Streptomyces gene replacement approach to Amycolatopsis mediterranei S699 and further on the implementation of genetic modifications that enable an increased production of the derivative 24-desmethyl rifamycin B in the mutant strain DCO36. The described genetic modifications resulted in a mutant strain of DCO36 with rifQ deletion showing a 62% increase in 24-desmethyl rifamycin B production, while a mutant with rifO overexpression showed a 27% increase.

Background: The coexistence of lung cancer and tuberculosis is not rare. Rifamycin plays a pivotal role in anti-tuberculosis therapy. However, its potential impact on the liver metabolism of oncology drugs raises concerns. We performed this study to explore whether Rifamycin affects the survival of patients with tuberculosis and lung cancer. Methods: Drawing from the Taiwan National Health Insurance Research Database, we identified patients diagnosed with concurrent lung cancer and tuberculosis between 2000 and 2014. Patients were categorized based on whether they underwent rifamycin-inclusive or rifamycin-exempt anti-tuberculosis therapy. Subsequently, we paired them at a 1:1 ratio and evaluated the mortality risk over a two-year span. Results: Out of the study participants, 1558 (81.4%) received rifamycin-based anti-tuberculosis therapy, while 356 (18.6%) underwent a rifamycin-free regimen. Analysis revealed no marked variance in the biennial mortality rate between the groups (adjusted hazard ratio: 1.33, 95% confidence interval 0.93–1.90, p = 0.1238). When focusing on the matched sets comprising 127 individuals in each group, the data did not indicate a significant link between rifamycin and a heightened two-year mortality risk (adjusted hazard ratio: 1.00, 95% confidence interval 0.86–1.18, p = 0.9538). Conclusions: For individuals with concomitant lung cancer and tuberculosis, rifamycin's administration did not adversely influence two-year survival. Thus, rifamycin-containing anti-TB regimens should be prescribed for the indicated patients. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains the leading cause of death among people with human immunodeficiency virus (PWH). The diagnosis of latent TB infection (LTBI) and treatment with TB preventative therapy (TPT) can reduce morbidity and mortality in this population. Historically, isoniazid has been recommended for TPT in PWH due to the absence of drug-drug interactions with most antiretroviral therapy (ART). However, newer rifamycin-based regimens are safer, shorter in duration, associated with improved adherence, and may be as or more effective than isoniazid TPT. Current guidelines have significant heterogeneity in their recommendations for TPT regimens and acceptability of drug interactions with modern ART. In this Infectious Diseases learning unit, we review common questions on diagnosis, treatment, and drug interactions related to the management of LTBI among PWH.

Various types of otitis are common in the pediatric population. The use of otoscopy techniques by primary care doctors (pediatricians, family, and general practitioners) has significantly expanded the diagnostic capabilities of the primary examination of the child. However, it requires many specialists to know the principles of patient management with various types of otitis media. The article addresses the principles of routing and drug therapy for patients with various types of otitis media. The focus is on ear drops (formulation, indications for using specific drugs, safety, and age-related aspects).

Eight rifamycin-related polyketides were isolated from the culture broth of a marine-derived bacterium Salinispora arenicola, including five known (2–5 and 8) and three new derivatives (1, 6, and 7). The structures of the new compounds were determined by means of spectroscopic methods (HRESIMS and 1D, 2D NMR) and a comparison of their experimental data with those previously reported in the literature. The isolated compounds were evaluated for their cytotoxicity against one normal, six solid, and seven blood cancer cell lines and 1 showed moderate activity against all the tested cell lines with GI50 values ranging from 2.36 to 9.96 µM. [ABSTRACT FROM AUTHOR]

Objective: The effect of subcutaneous rifampicin administration on postoperative early wound discharge in patients undergoing hemiarthroplasty after femoral neck fracture was investigated. Methods: Between 2013 and 2015, 58 (36 female, 22 male) patients aged 65-94 (mean 79.29±7.99 years) who underwent hemiarthroplasty for hip fracture were included in the study. Two of the patients were Garden type 2, 21 were Garden type 3 and 35 were Garden type 4. The patients were followed from the postoperative period until discharge, and the length of stay was recorded. The subcutaneous rifamycin-administered group (group 1), saline irrigation-only group (group 2), and saline solution-added rifamycin group (group 3) were examined in 3 groups. Results: The duration of discharge was statistically significant according to age (p<0.05). The mean duration of wound discharge was significantly higher in patients older than 75 years (p=0.02). The operation duration of RIF + SF irrigation was significantly higher than that of SF irrigation (p=0.037). There was no statistically significant relationship between operation duration, incision length and additional diseases, and discharge time (p>0.05). Conclusion: There was no significant difference between the groups in terms of postoperative discharge times. The operative time was longer in patients who received subcutaneous rifamycin and were older than 75 years. Additional or isolated rifamycin application for hip hemiarthroplasty irrigation has no superiority over the saline solution. [ABSTRACT FROM AUTHOR]

Tesemma Sileshi,1,2 Gosaye Mekonen,1 Eyasu Makonnen,2,3 Eleni Aklillu4 1Department of Pharmacy, Ambo University, Ambo, Ethiopia; 2Department of Pharmacology and Clinical Pharmacy, Addis Ababa University, Addis Ababa, Ethiopia; 3Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), Addis Ababa University, Addis Ababa, Ethiopia; 4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenCorrespondence: Tesemma Sileshi, Department of Pharmacy, Ambo University, P.O Box 19, Ambo, Ethiopia, Tel +2510911550975, Email tesemmasileshi@gmail.comAbstract: Background: Rifamycins are a novel class of antibiotics clinically approved for tuberculosis chemotherapy. They are characterized by high inter-individual variation in pharmacokinetics. This systematic review aims to present the contribution of genetic variations in drug-metabolizing enzymes and transporter proteins to the inter-individual variation of rifamycin pharmacokinetics.Method: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. The search for relevant studies was done through PubMed, Embase, Web of Science, and Scopus databases. Studies reporting single nucleotide polymorphism in drug transporters and metabolizing enzymes’ influence on rifamycin pharmacokinetics were solely included. Two reviewers independently performed data extraction.Results: The search identified 117 articles of which 15 fulfilled the eligibility criteria and were included in the final data synthesis. The single nucleotides polymorphism in the drug transporters SLCO1B1 rs4149032, rs2306283, rs11045819, and ABCB1 rs1045642 for rifampicin, drug metabolizing enzyme AADAC rs1803155 for rifapentine and CES2 c.-22263A>G (g.738A>G) for rifampicin partly contributes to the variability of pharmacokinetic parameters in tuberculosis patients.Conclusion: The pharmacokinetics of rifamycins is influenced by genetic variation of drug-metabolizing enzymes and transporters. Controlled clinical studies are, however, required to establish these relationships.Keywords: rifamycin, pharmacokinetics, pharmacogenetics, enzymes, transporters

Background: The coexistence of lung cancer and tuberculosis is not rare. Rifamycin plays a pivotal role in anti-tuberculosis therapy. However, its potential impact on the liver metabolism of oncology drugs raises concerns. We performed this study to explore whether Rifamycin affects the survival of patients with tuberculosis and lung cancer. Methods: Drawing from the Taiwan National Health Insurance Research Database, we identified patients diagnosed with concurrent lung cancer and tuberculosis between 2000 and 2014. Patients were categorized based on whether they underwent rifamycin-inclusive or rifamycin-exempt anti-tuberculosis therapy. Subsequently, we paired them at a 1:1 ratio and evaluated the mortality risk over a two-year span. Results: Out of the study participants, 1558 (81.4%) received rifamycin-based anti-tuberculosis therapy, while 356 (18.6%) underwent a rifamycin-free regimen. Analysis revealed no marked variance in the biennial mortality rate between the groups (adjusted hazard ratio: 1.33, 95% confidence interval 0.93–1.90, p = 0.1238). When focusing on the matched sets comprising 127 individuals in each group, the data did not indicate a significant link between rifamycin and a heightened two-year mortality risk (adjusted hazard ratio: 1.00, 95% confidence interval 0.86–1.18, p = 0.9538). Conclusions: For individuals with concomitant lung cancer and tuberculosis, rifamycin’s administration did not adversely influence two-year survival. Thus, rifamycin-containing anti-TB regimens should be prescribed for the indicated patients.

Rifamycin antibiotics are a valuable class of antimicrobials for treating infections by mycobacteria and other persistent bacteria owing to their potent bactericidal activity against replicating and non‐replicating pathogens. However, the clinical utility of rifamycins against Mycobacterium abscessus is seriously compromised by a novel resistance mechanism, namely, rifamycin inactivation by ADP‐ribosylation. Using a structure‐based approach, we rationally redesign rifamycins through strategic modification of the ansa‐chain to block ADP‐ribosylation while preserving on‐target activity. Validated by a combination of biochemical, structural, and microbiological studies, the most potent analogs overcome ADP‐ribosylation, restored their intrinsic low nanomolar activity and demonstrated significant in vivo antibacterial efficacy. Further optimization by tuning drug disposition properties afforded a preclinical candidate with remarkable potency and an outstanding pharmacokinetic profile. [ABSTRACT FROM AUTHOR]

Eight rifamycin-related polyketides were isolated from the culture broth of a marine-derived bacterium Salinispora arenicola, including five known (2–5 and 8) and three new derivatives (1, 6, and 7). The structures of the new compounds were determined by means of spectroscopic methods (HRESIMS and 1D, 2D NMR) and a comparison of their experimental data with those previously reported in the literature. The isolated compounds were evaluated for their cytotoxicity against one normal, six solid, and seven blood cancer cell lines and 1 showed moderate activity against all the tested cell lines with GI50 values ranging from 2.36 to 9.96 µM.

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The divalproex (DVP) package insert states that rifampin may increase the oral clearance of valproate by 40% and that valproic acid derivative dose adjustments may be required when starting or stopping rifampin. However, the overall clinical significance of this drug-drug interaction remains unclear given that limited clinical outcome data has been published. This case describes a 52-year-old female with bipolar disorder, borderline personality disorder, and PTSD who was previously stable on a medication regimen consisting of DVP delayed-release 500 mg every morning and 1500 mg every evening (baseline steady-state trough 99.8 mcg/mL). Throughout rifampin therapy for latent tuberculosis treatment, she required an increase in both the frequency of DVP administration, from 2 to 3 times daily, and DVP dose by 75% to maintain clinical stability. Valproic acid trough concentrations ranged from 56.4 to 75.9 mcg/mL during the 4-month course of rifampin. This report supports that the DVP-rifampin interaction may be clinically significant and of a greater magnitude than suggested by the package insert.

Objectives: To assess differential effects of different materials combined with allograft on bone-to-implant contact and newly formed bone formation in dental implants with coronal defects histomorphometrically. Materials and Methods: The study was conducted on 24 male New Zealand white rabbits. Dental implants (3.0 × 10 mm) were placed at the center of defects (9 mm diameter, 4 mm depth) created in the tibial bones of the rabbits. Graft (GF, n=8), graft + rifamycin (GR, n=8), and graft + black cumin oil via orogastric route (GB, n=8) were applied on the coronal aspects of the implants for 28 days. Undecalcified histomorphometric analyses were conducted on slides stained with toluidine blue. Results: Bone-to-implant contact was 46.57% ± 3.59% in the graft, 67.12% ± 3.64% in the graft+rifamycin, and 55.62% ± 4.37% in the graft+black cumin oil groups. The percentage of new bone formation at the defect area was 34.71% ± 4.11% in the graft, 55.37% ± 4.89% in the graft + rifamycin, and 45.75% ± 3.69% in the graft + black cumin oil groups. In terms of new bone formation and bone-to-implant contact, graft + rifamycin and graft + black cumin oil groups were significantly different from the graft group. The differences between the graft + rifamycin and graft + black cumin oil groups were also statistically significant. Conclusion: Allogreft + rifamycin and orogastric black cumin oil were found to have positive effects on bone healing at sites with coronal defects. Rifamycin showed significantly greater favorable effects on bone-to-implant contact and new bone formation compared to black cumin oil.

Purpose: This study aimed to evaluate the efficacy of a single-dose topical rifamycin application on postoperative complications after impacted lower third molar surgery., Materials and Methods: This prospective, controlled clinical study consisted of individuals with bilaterally impacted lower third molars that would be extracted for orthodontic reasons. The extraction sockets were irrigated with 3 ml/250 mg of rifamycin solution in Group 1, while in Group 2 (control group) the extraction sockets were irrigated with 20 ml of physiological saline. Pain intensity was measured daily for 7 days by using visual analog scale. Trismus and edema were evaluated preoperatively and on the postoperative days 2 and 7 by calculating the proportional changes in maximum mouth opening and mean distance between reference points of the face, respectively. Paired samples t-test, Wilcoxon signed rank test and Chi-square test were used to analyze the study variables., Results: 35 patients (19 female, 16 male) were included in the study. The mean age of all participants was 22.19±4.98. Alveolitis was observed in 8 patients, (6 in the control group, 2 in the rifamycin group). There was no statistically significant difference between groups in terms of trismus and swelling measurements on the 2nd and 7th postoperative days (p>0.05). VAS scores were significantly low in rifamycin group on postoperative days 1 and 4 (p<0.05)., Conclusion: Within the limits of the present study, topical rifamycin application reduced the incidence of alveolitis, prevented infection, and provided analgesic effect after surgical removal of impacted third molars., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Introduction: Short‐course preventive therapy with 1‐month course of daily administration of isoniazid (300‐mg) plus rifapentine (600‐mg) (1HP) and 3‐month course of weekly administration of isoniazid (900‐mg) plus rifapentine (900‐mg) (3HP) has higher completion rates than 9‐month course of daily isoniazid (9H) for individuals with latent tuberculosis infection (LTBI). We aimed to evaluate the effect, safety and tolerability of 1HP in people living with HIV (PLWH) and LTBI who received coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Methods: PLWH testing positive by interferon‐gamma release assay and having received BIC/FTC/TAF for >2 weeks with plasma HIV RNA load (PVL) <200 copies/ml were enrolled. BIC trough plasma concentrations and cytokine profiles were determined before the first dose (day 1/baseline), 24 h after the 14th (day 15) and 28th (day 29) doses of 1HP. PVL were determined on days 15 and 29 of 1HP and every 3 months subsequently after discontinuation of 1HP. Results: From November 2019 to December 2020, 48 PLWH with LTBI were enrolled. One participant (2.1%) discontinued 1HP on day 15 due to fever and generalized rashes with PVL of 72 copies/ml, which was <50 copies/ml in three subsequent determinations while on BIC/FTC/TAF over the 12 months of follow‐up. The percentages of BIC trough plasma concentrations above the protein‐adjusted 95% effective concentration (paEC95 = 162 ng/ml) were 56.3% and 37.0% on days 15 and 29, respectively. The percentage of PVL <200 copies/ml was 91.7% on day 15, 97.8% on day 29 and 100% at both months 3 and 6. After a median observation of 52 weeks (interquartile range, 51–55), all participants continued BIC/FTC/TAF with a median PVL of 20 copies/ml (range 20–331). Except for the participant who discontinued 1HP because of allergic reactions, none of the participants had relevant symptoms or increases of the cytokine levels assessed between baseline and days 15 and 29 of 1HP. Conclusions: BIC/FTC/TAF in combination with 1HP was well tolerated with a high completion rate. BIC trough plasma concentrations were significantly decreased with concurrent use of 1HP among PLWH with LTBI. While transient viral blips were observed during 1HP without causing subsequent treatment failure, such combination should be applied with caution. [ABSTRACT FROM AUTHOR]

This review summarizes the literature data reported from 2000 up to the present on the development of various electrochemical (voltammetric, amperometric, potentiometric and photoelectrochemical), optical (UV-Vis and IR) and luminescence (chemiluminescence and fluorescence) methods and the corresponding sensors for rifamycin antibiotics analysis. The discussion is focused mainly on the foremost compound of this class of macrocyclic drugs, namely rifampicin (RIF), which is a first-line antituberculosis agent derived from rifampicin SV (RSV). RIF and RSV also have excellent therapeutic action in the treatment of other bacterial infectious diseases. Due to the side-effects (e.g., prevalence of drug-resistant bacteria, hepatotoxicity) of long-term RIF intake, drug monitoring in patients is of real importance in establishing the optimum RIF dose, and therefore, reliable, rapid and simple methods of analysis are required. Based on the studies published on this topic in the last two decades, the sensing principles, some examples of sensors preparation procedures, as well as the performance characteristics (linear range, limits of detection and quantification) of analytical methods for RIF determination, are compared and correlated, critically emphasizing their benefits and limitations. Examples of spectrometric and electrochemical investigations of RIF interaction with biologically important molecules are also presented.

ABSTRACT After staphylococci, streptococci and enterococci are the most frequent causes of periprosthetic joint infection (PJI). MICs and minimum biofilm bactericidal concentrations of rifampin, rifabutin, and rifapentine were determined for 67 enterococcal and 59 streptococcal PJI isolates. Eighty-eight isolates had rifampin MICs of ≤1 μg/ml, among which rifabutin and rifapentine MICs were ≤ 8 and ≤4 μg/ml, respectively. There was low rifamycin in vitro antibiofilm activity except for a subset of Streptococcus mitis group isolates. IMPORTANCE Rifampin is an antibiotic with antistaphylococcal biofilm activity used in the management of staphylococcal periprosthetic joint infection with irrigation and debridement with component retention; some patients are unable to receive rifampin due to drug interactions or intolerance. We recently showed rifabutin and rifapentine to have in vitro activity against planktonic and biofilm states of rifampin-susceptible periprosthetic joint infection-associated staphylococci. After staphylococci, streptococci and enterococci combined are the most common causes of periprosthetic joint infection. Here, we investigated the in vitro antibiofilm activity of rifampin, rifabutin, and rifapentine against 126 Streptococcus and Enterococcus periprosthetic joint infection isolates. In contrast to our prior findings with staphylococcal biofilms, there was low antibiofilm activity of rifampin, rifabutin, and rifapentine against PJI-associated streptococci and enterococci, apart from some Streptococcus mitis group isolates.

A mutant of Mycobacterium smegmatis is a potential class I model substitute for Mycobacterium tuberculosis. Because not all of the rifamycins have been tested in this organism, we determined bactericidal profiles for the 6 major rifamycin derivatives. The profiles closely mirrored those established for M. tuberculosis. Rifalazil was confirmed to be the most potent rifamycin. Because the tuberculous granuloma presents a harshly oxidizing environment we explored the effects of oxidation on rifamycins. Mass spectrometry confirmed that three of the six major rifamycins showed autoxidation in the presence of trace metals. Oxidation could be monitored by distinctive changes including isosbestic points in the ultraviolet-visible spectrum. Oxidation of rifamycins abrogated anti-mycobacterial activity in M. smegmatis. Protection from autoxidation was conferred by binding susceptible rifamycins to tear lipocalin, a promiscuous lipophilic protein. Rifalazil was not susceptible to autoxidation but was insoluble in aqueous solution. Solubility was enhanced when complexed to tear lipocalin and was accompanied by a spectral red shift. The positive solvatochromism was consistent with robust molecular interaction and binding. Other rifamycins also formed a complex with lipocalin, albeit to a lesser extent. Protection from oxidation and enhancement of solubility with protein binding may have implications for delivery of select rifamycin derivatives.

Background Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis. Methods Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively. Results Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P  ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group. Conclusions Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections. [ABSTRACT FROM AUTHOR]

Amycolatopsis mediterranei S699 produces rifamycin B and successors of this strain are in use for the industrial production of rifamycin B. Semisynthetic derivatives of rifamycin B are used against Mycobacterium tuberculosis that causes tuberculosis. Although the rifamycin biosynthetic gene cluster was characterized two decades ago, the regulation of rifamycin B biosynthesis in Amycolatopsis mediterranei S699 is poorly understood. In this study, we analysed the genome and proteome of Amycolatopsis mediterranei S699 and identified 1102 transcription factors which comprise about 10% of the total genome. Using interactomics approaches we delineated 30 unique transcription factors directly involved in secondary metabolism that regulate rifamycin B biosynthesis. We also predict the role of RifN as hub in controlling the regulation of other genes involved in rifamycin biosynthesis. RifN is important for maintaining the integrity of the rifamycin-network. Thus, these transcription factor can be exploited to improve rifamycin B production in Amycolatopsis mediterranei S699. [ABSTRACT FROM AUTHOR]

This article reviews seven drugs recently approved by the FDA, including indications, precautions, adverse reactions, and nursing considerations. [ABSTRACT FROM AUTHOR]

Abstract Background Due to the important role of rifamycin in curing tuberculosis infection, the study on rifamycin has never been stopped. Although RifZ, which locates within the rifamycin biosynthetic cluster, has recently been characterized as a pathway-specific regulator for rifamycin biosynthesis, little is known about the regulation of rifamycin export. Results In this work, we proved that the expression of the rifamycin efflux pump (RifP) was regulated by RifQ, a TetR-family transcriptional regulator. Deletion of rifQ had little impact on bacterial growth, but resulted in improved rifamycin production, which was consistent with the reverse transcription PCR results that RifQ negatively regulated rifP’s transcription. With electrophoretic mobility shift assay and DNase I Footprinting assay, RifQ was found to directly bind to the promoter region of rifP, and a typical inverted repeat was identified within the RifQ-protected sequences. The transcription initiation site of rifP was further characterized and found to be upstream of the RifQ binding sites, well explaining the RifQ-mediated repression of rifP’s transcription in vivo. Moreover, rifamycin B (the end product of rifamycin biosynthesis) remarkably decreased the DNA binding affinity of RifQ, which led to derepression of rifamycin export, reducing the intracellular concentration of rifamycin B as well as its toxicity against the host. Conclusions Here, we proved that the export of rifamycin B was repressed by RifQ in Amycolatopsis mediterranei, and the RifQ-mediated repression could be specifically relieved by rifamycin B, the end product of rifamycin biosynthesis, based on which a feedback model was proposed for regulation of rifamycin export. With the findings here, one could improve the antibiotic yield by simply inactivating the negative regulator of the antibiotic transporter.

Chunlan Zheng,1,* Xiufen Hu,2,* Li Zhao,1 Minhui Hu,1 Feng Gao3 1Department of Internal Medicine – Section 5, Wuhan Pulmonary Hospital (Wuhan Tuberculosis Control Institute), 2Department of Paediatrics, Tongji Hospital, 3Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Rifapentine is a rifamycin derivate approved by the US Food and Drug Administration in 1998 for the treatment of active, drug-susceptible tuberculosis (TB). In 2014, rifapentine was approved for the treatment of latent TB infection in patients at high risk of progression to active disease and is currently under evaluation by the European Medicines Agency. Expanding indications of rifapentine largely affect diabetes patients, since about one-third of them harbor latent TB. Clinical consequences of rifapentine use in this population and potentially harmful interactions with hypoglycemic agents are widely underexplored and generally considered similar to the ones of rifampicin. Indeed, rifapentine too may decrease blood levels of many oral antidiabetics and compete with them for protein-binding sites and/or transporters. However, the two drugs differ in protein-binding degree, the magnitude of cytochrome P450 induction and auto-induction, the degree of renal elimination, and so on. Rifapentine seems to be more suitable for use in diabetes patients with renal impairment, owing to the fact that it does not cause renal toxicity, and it is eliminated via kidneys in smaller proportions than rifampicin. On the other hand, there are no data related to rifapentine use in patients >65 years, and hypoalbuminemia associated with diabetic kidney disease may affect a free fraction of rifapentine to a greater extent than that of rifampicin. Until more pharmacokinetic information and information on the safety of rifapentine use in diabetic patients and drug–drug interactions are available, diabetes in TB patients treated with rifapentine should be managed with insulin analogs, and glucose and rifapentine plasma levels should be closely monitored. Keywords: rifamycin, antituberculosis treatment, glucose intolerance, hyperglycemia, safety

Objective:This study aimed to investigate possible ototoxicity associated with topical rifamycin application via electrophysiological tests and ultrastructural examinations.Methods:Electrophysiological assessment was performed with tympanometry, auditory brainstem response (ABR), and distortion product otoacoustic emission (DPOAE) measurements. This study was conducted on 40 ears of 20 guinea pigs that were detected to have normal hearing thresholds. The animals were randomly assigned to three groups: Group 1 (n=12) received 0.1 mL rifamycin, Group 2 (n=8) received 0.1 ml gentamycin, and Group 3 (n=20) received 0.1 mL physiological saline. The antibiotics and saline solutions were administered via intratympanic injections. After five injections every other day, electrophysiological tests were performed again on the 15th day. After electrophysiological measurements, the temporal bones of all guinea pigs were prepared for ultrastructural examinations and the cochlear surface morphology was examined by scanning electron microscopy (SEM).Results:The animals in group 3 did not show a statistically significant change in their DPOAE signal/noise ratio (SNR) or ABR thresholds (p>0.05). In groups 1 and 2, the reduction in the DPOAE SNR and the increase in the ABR threshold were statistically significant (p0.05).Conclusion:The results indicate that rifamycin application to the middle ears of guinea pigs has mild ototoxic effects on their inner ears.

Objectives: The aim of this study was to evaluate effect of local rifamycin application on BMP-2 expression and bone healing.Materials and Methods: A standardized 5.0-mm- diameter critical size bone defect was created mandible angulus region. In the control group (8 rats) defects were left empty. In the Group 1 (n=8 rats) defect was irrigated with rifamycin solution and 25 mg rifamycin solution injected defect area at 1, 3, 7 days after surgery. In the group 2 (n=8 rats) defects were grafted with a gelatin sponge mixed 25 mg rifamycin solution. Rats were sacrificed at 21 days after surgery. Histological slides were prepared from defect site for both immunohistochemical analysis (bone morphogenetic protein-2 (BMP-2) antibody) and histomorphometric analysis. Data were analyzed using Mann Whitney U and Kruskall Wallis test.Results: The average new bone formation, number of osteoblast and new vessel formation count were increased more in both of experimental groups in comparison with control group. Anti-BMP-2 labelling (Cell count) was increased more in both of experimental groups in comparison with control group. Conclusion: Local rifamycin application has positive effects on BMP-2 expression and bone regeneration at critical sized bone defects.

Objective: To evaluate the potential of platelet-rich fibrin (PRF) and rifamycin to enhance guided bone augmentation with simultaneous high-profile dental implant placement in a rabbit tibia model. Materials and Methods: Dental implants protruding 2 mm were covered with dome-shaped stiff occlusive titanium barriers filled with demineralized freeze-dried bone allograft (DFDBA)+saline (7 rabbits), DFDBA + rifamycin (8 rabbits), or DFDB +PRF (8 rabbits). After 4 weeks, the animals were sacrificed, and undecalcified histomorphometric examination with toluidine blue staining was performed. Results: The bone-to-implant contact (BIC) was 58.43 ± 1.92% in the saline group, 68.3 ±20.37% in the rifamycin group, and 80.70±2.55% in the PRF group, and the percentage of new bone formation was 36.90 ± 0.94%, 45.26±0.60%, and 51.82±0.82%, respectively. Conclusions: Both PRF and rifamycin have potential to enhance GBA, and using DFDBA + PRF or DFDBA+rifamycin beneath a stiff occlusive titanium barrier next to a high-profile implant may enhance both BIC and new bone formation. Keywords: Guided bone augmentation, platelet-rich fibrin, rifamycin, allograft, high-profile dental implants

BACKGROUND Rifamycins are a group of antibiotics mainly used in the treatment of tuberculosis (TB), however they interact with antiretroviral therapy (ART). Rifabutin allows more regimens options for concomitant imunodeficiency virus (HIV) treatment compared to rifampicin. OBJECTIVE Compare the outcomes of TB-HIV co-infected patients who used rifampicin or rifabutin. METHODS We analysed data from a prospective cohort study at National Institute of Infectious Diseases Evandro Chagas, Rio de Janeiro (RJ), Brazil. Patients who were treated for TB and HIV with rifampicin or rifabutin, from February 2011 to September 2016 were included. FINDINGS There were 130 TB-HIV patients, of whom 102 were treated with rifampicin and 28 with rifabutin. All patients in the rifabutin-treated group and 55% of the rifampicin-treated group patients were ART-experienced. Patients treated with rifampicin had similar abandon and cure rates, interruptions in treatment due to adverse reactions, immune reconstitution inflammatory syndrome and a similar mortality rate as those treated with rifabutin. However, rifampicin-treated patients had higher CD4 counts and more frequently undetectable HIV viral load by the end of treatment (67% versus 18%, p < 0.001) compared to rifabutin-treated patients, even when only ART-experienced patients were evaluated (66,6% versus 36,3%, p = 0.039). CONCLUSIONS Patients who used rifabutin had worst immune and virological control. This group had more ART-experienced patients. New and simpler regimens are needed for patients who do not respond to previous antiretroviral therapies.

Excessive bacteria and nutrient malabsorption are the two major events need to clarify small intestinal bacterial overgrowth (SIBO). Clinically, SIBO is defined as a condition with the existence of > 106 colony-forming units (CFU) bacteria in the human intestine. It is the only generally accepted criteria to diagnose the SIBO in clinical practice. The main problem is that several clinical disorders are happening in patients with SIBO; thus actual discrimination will be relatively difficult. Exploration of the current status of SIBO management and suggesting rifaximin as a main clinical target is our optimal goal. Although the quality of performed randomized clinical trials needs to be re-evaluated, rifaximin seems the only suitable option for treatment of SIBO. Undoubtedly, new treatment should include the correction of ongoing small intestinal microflora with proper antibiotic therapy. Personalized medicine is another option that should be studied thoroughly before entering the area of SIBO treating using proton pump inhibitors. Finally, we have to focus on the available option to have better management of patients with SIBO. [ABSTRACT FROM AUTHOR]

Clostridioides difficile is a colonizer of the human gut; asymptomatic colonization has been reported to be more common in infants and is highly variable across regions even with no symptoms of diarrhea or death. Antibiotic treatment strategies might increase the antibiotic resistance of C. difficile. We performed a one-point study involving 1098 healthy infants (0–36 months) to address the deficiency of reports on C. difficile colonization in Chinese community infants. The C. difficile colonization rate was 22.8% (250/1098), and more than half of the strains (55.2%) were toxigenic isolates. Among the 138 toxigenic isolates, 111 were of the A+B+CDT– genotype, 26 strains were A–B+CDT–, and one strain was A+B+CDT+. Fifteen different PCR ribotypes were found among the 250 isolates, and PCR-ribotype HB03 appeared to be dominant type, accounting for 19.6% (49/250). High levels of resistance to antimicrobial agents were observed. Our study showed that age and hospitalization before stool collection were positively correlated with the C. difficile colonization rate, whereas the delivery term was negatively related to the colonization rate. Particular attention should be paid to the increasing resistance of C. difficile to rifamycin. • C. difficile strain carriage rates were positively correlated with age in infants under 3 years old. • Delivery term and hospitalization were associated with the colonization rate. • Particular attention should be paid to the resistance to rifamycin in C. difficile. [ABSTRACT FROM AUTHOR]

The study aims to assess the effects of antibiotics (ABs), which are typically used in spinal infection prophylaxis, on the formation of epidural fibrosis (EF). Specifically, we investigated the effect of rifamycin and gentamycin on EF formation in laminectomized rats. Thirty-two rats were randomly and equally divided into four groups as follows: laminectomy and physiological saline (0.9% NaCl) solution (control); laminectomy and rifamycin; laminectomy and gentamicin; and laminectomy and a mixture of rifamycin and gentamicin. Laminectomy was performed on L1 and L2 vertebrae in all rats. One month after spinal surgery, spinal tissue samples surrounding the laminectomy were cut with a microtome and stained with hematoxylin-eosin and Masson's trichrome. The histopathological analysis included examining the extent of EF, fibroblast cell density, and cartilage and bone regeneration. Statistical analysis was performed using the IBM SPSS Statistics 22 program (SPSS IBM, Turkey). A value of p < 0.05 was considered statistically significant. EF value differences between the AB treatment groups and the control group were statistically significant (p = 0.030). Specifically, binary comparisons indicated that the EF value was significantly higher in the rifamycin group than that in the control group (p = 0.003; p < 0.05). Our study suggests that locally applied ABs, especially rifamycin, should be diluted before administration to the epidural space. [ABSTRACT FROM AUTHOR]

A number of strategies have been developed to mine novel natural products based on biosynthetic gene clusters and there has been dozens of successful cases facilitated by the development of genomic sequencing. During our study on biosynthesis of the antitumor polyketide kosinostatin (KST), we found that the genome of Micromonospora sp. TP-A0468, the producer of KST, contains other potential polyketide gene clusters, with no encoded products detected. Deletion of kst cluster led to abolishment of KST and the enrichment of several new compounds which were isolated and characterized as 16-demethylrifamycins (3-6). Transcriptional analysis demonstrated that the expression of the essential genes related to the biosynthesis of 3-6 was in comparable level in wild type and kst cluster deletion strain. This indicates that the accumulation of these compounds was due to the redirection of metabolic flux rather than transcriptional activation. Genetic disruption, chemical complementation and bioinformatic analysis revealed that the production of 3-6 was accomplished by crosstalk between two distantly placed polyketide gene clusters pks3 and M-rif. This finding not only enriches the analogue pool and biosynthetic diversity of rifamycins, but also provides an auxiliary strategy for natural product discovery through genome mining in polyketide-producing microorganisms. Importance Natural products are essential in the development of novel clinically-used drugs. Discovering new natural products and modifying known compounds are still the two main ways to generate new 37 candidates. Here, we have discovered several rifamycins with varied skeleton by redirecting the metabolic flux from the predominant polyketide biosynthetic pathway to the rifamycin pathway in the marine actinomycetes species Micromonospora sp. TP-A0468. Rifamycins are indispensable chemotherapeutics in the treatment of various diseases such as tuberculosis, leprosy and AIDS-related mycobacterial infections. This work exemplifies a useful method for the discovery of cryptic natural products in genome-sequenced microbes. Moreover, the 16-demethylrifamycins and their genetically manipulable producer provides a new opportunity in the construction of novel rifamycin derivates to aid in the defense against the ever-growing drug-resistance of Mycobacterium tuberculosis. [ABSTRACT FROM AUTHOR]

Abstract Clostridium difficile infection (CDI) is an increasingly common occurrence in the hospital setting, and it is associated with significant morbidity and mortality. In vitro studies have found that rifaximin, a nonabsorbable rifamycin antibiotic, displays potent antimicrobial activity against C. difficile. This systematic review thus aimed to examine the clinical role of rifaximin in CDI. Using the keywords [clostridium OR difficile OR colitis] AND [rifaximin OR xifaxan OR rifagut], a preliminary search on the PubMed, EMBASE, Medline, Clinicaltrials.gov and Google Scholar databases yielded 6210 papers published in English between 1-Jan-1988 and 1-Jul-2018. A total of eight clinical trials were systematically reviewed. Of these, only two were randomized, controlled trials. In the treatment of mild-moderate CDI, rifaximin is a viable alternative to existing therapies (metronidazole or vancomycin). More importantly, rifaximin has a potential role in conjunction with other therapies, showing to be efficacious in reducing the rate of CDI recurrence. However, clinical studies have reported a resistance rate in the range of 29.1–48.9%, with a geographical variance in the distribution of rifaximin-resistant C. difficile strains. With its unique eubiotic properties and positive modulation of the gut flora, rifaximin has a potential therapeutic role in the management of CDI, especially in CDI recurrences. As there is a paucity of randomized, controlled trials to support its use, studies with larger and more diverse populations should be conducted before the efficacy of rifaximin can be conclusively stated. Rifaximin is also a relatively expensive antimicrobial, further studies should include cost-benefit analyses. Highlights • This is the first systematic review to examine the use of rifaximin for C. difficile infections (CDI). • 8 clinical trials were systematically reviewed. • Rifaximin is a viable alternative for CDI. • It also shows efficacy in reducing the recurrence of CDI. • Further detailed trials and cost-benefit analyses are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Information on the long-term treatment outcome following nontuberculous mycobacterial (NTM) lymphadenitis is very limited. We performed a study to (a) compare cure rates following different initial treatment courses, (b) describe subsequent treatment courses and their outcomes, and (c) determine the occurrence of late sequelae in immunocompetent children with NTM lymphadenitis. Materials and Methods: In 2011, we conducted a retrospective follow-up study in 71 parents whose children had been hospitalized with NTM disease 2002–2005. A telephone survey was performed using a standardized questionnaire to collect information on the therapeutic management and treatment outcome. Results: Of 61 children with NTM lymphadenitis, 33 (54%) children were cured after the initial treatment. We found no significant difference in cure rates following surgical intervention only (45%, 13/29 children) and a combination of surgical intervention and chemotherapy (61%, 19/31 children). In 7 out of 11 children, the cure rate following complete lymph node excision was 64%. Subsequent courses of treatment including repeated surgical intervention, combination therapy, chemotherapy only, and wait-and-see strategy in children where initial therapy failed resulted in the cure of all 61 children. In four children (7%), recurrences were observed up to 5 years later. Conclusions: Our study showed that recurrent NTM lymphadenitis might be observed several years after initial resolution of disease. The cure rate following complete lymph node excision was lower than reported in other studies. Subsequent treatment courses were necessary in half of the children. Physicians and parents need to be aware that NTM lymphadenitis in children requires careful choice of intervention and active follow-up.

Proansamycin X, a hypothetical earliest macrocyclic precursor in the biosynthesis of rifamycin, had never been isolated and identified. According to bioinformatics analysis, it was proposed that RifT (a putative NADH-dependent dehydrogenase) may be a candidate target responsible for the dehydrogenation of proansamycin X. In this study, the mutant strain Amycolatopsis mediterranei S699 ΔrifT was constructed by deleting the rifT gene. From this strain, eleven 8-deoxy-rifamycin derivatives (1–11) and seven known analogues (12–18) were isolated. Their structures were elucidated by extensive analysis of 1D and 2D NMR spectroscopic data and high-resolution ESI mass spectra. Compound 1 is a novel amide N-glycoside of seco-rifamycin. Compounds 2 and 3 feature conserved 11,12-seco-rifamycin W skeleton. The diverse post-modifications in the polyketide chain led to the production of 4–11. Compounds 2, 3, 5, 6, 13 and 15 exhibited antibacterial activity against Staphylococcus aureus (MIC (minimal inhibitory concentration) values of 10, 20, 20, 20, 40 and 20 μg/mL, respectively). Compounds 14, 15, 16, 17 and 18 showed potent antiproliferative activity against KG1 cells with IC50 (half maximal inhibitory concentration) values of 14.91, 44.78, 2.16, 18.67 and 8.07 μM, respectively.

Mycobacterium abscessus is the most difficult-to-treat nontuberculous mycobacteria because of its resistance to many antibiotics. In this study, we screened the Korea Chemical Bank library for a bioluminescent reporter assay to identify molecules capable of acting against M. abscessus. On application of the assay, rifamycin O showed excellent in vitro activity with a narrow range of the minimum inhibitory concentration required to inhibit the growth of 90% of the bacterium (MIC90 = 4.0–6.2 μM); its in vivo efficacy in the zebrafish (Danio rerio) infection model was comparable to that of rifabutin at 25 μM. Furthermore, rifamycin O did not show significant toxicity in cells and the zebrafish model. These results are the first in vivo indication that rifamycin O may be a drug candidate for treating M. abscessus infections.

The success of the TB control program is hampered by the major issue of drug-resistant tuberculosis (DR-TB). The situation has undoubtedly been made more difficult by the widespread and multidrug-resistant (XDR) strains of TB. The modification of existing anti-TB medications to produce derivatives that can function on resistant TB bacilli is one of the potential techniques to overcome drug resistance affordably and straightforwardly. In comparison to novel pharmaceuticals for drug research and progress, these may have a better half-life and greater bioavailability, be more efficient, and serve as inexpensive alternatives. Mycobacterium tuberculosis , which is drugsusceptible or drug-resistant, is effectively treated by several already prescribed medications and their derivatives. Due to this, the current review attempts to give a brief overview of the rifampicin derivatives that can overcome the parent drug's resistance and could, hence, act as useful substitutes. It has been found that one-third of the global population is affected by M. tuberculosis . The most common cause of infection-related death can range from latent TB to TB illness. Antibiotics in the rifamycin class, including rifampicin or rifampin (RIF), rifapentine (RPT), and others, have a special sterilizing effect on M. tuberculosis . We examine research focused on evaluating the safety, effectiveness, pharmacokinetics, pharmacodynamics, risk of medication interactions, and other characteristics of RIF analogs. Drug interactions are especially difficult with RIF because it must be taken every day for four months to treat latent TB infection. RIF continues to be the gold standard of treatment for drug-sensitive TB illness. RIF's safety profile is well known, and the two medicines' adverse reactions have varying degrees of frequency. The authorized once-weekly RPT regimen is insufficient, but greater dosages of either medication may reduce the amount of time needed to treat TB effectively., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Excessive bacteria and nutrient malabsorption are the two major events need to clarify small intestinal bacterial overgrowth (SIBO). Clinically, SIBO is defined as a condition with the existence of > 106 colony-forming units (CFU) bacteria in the human intestine. It is the only generally accepted criteria to diagnose the SIBO in clinical practice. The main problem is that several clinical disorders are happening in patients with SIBO; thus actual discrimination will be relatively difficult. Exploration of the current status of SIBO management and suggesting rifaximin as a main clinical target is our optimal goal. Although the quality of performed randomized clinical trials needs to be re-evaluated, rifaximin seems the only suitable option for treatment of SIBO. Undoubtedly, new treatment should include the correction of ongoing small intestinal microflora with proper antibiotic therapy. Personalized medicine is another option that should be studied thoroughly before entering the area of SIBO treating using proton pump inhibitors. Finally, we have to focus on the available option to have better management of patients with SIBO. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate the effects of topical rifamycin SV application on epidural fibrosis formation in a rat model. Materials and methods: Between March 2015 and April 2015, a total of 20 Wistar rats were equally and randomly divided into laminectomy only group (control group) and laminectomy and rifamycin SV group (treatment group). Laminectomy was performed between L3-L5 in all rats. Surgical field was irrigated with 1 mL rifamycin SV (1 mL). After four weeks, vertebral columns of the rats were removed en bloc between the L1 and L5 levels, and epidural fibrosis and arachnoid involvement were histopathologically evaluated and graded. Results: Grade 3 epidural fibrosis formation ratio was lower in the treatment group (40%) compared to the control group (80%). However, there was no statistically significant difference between the treatment and control groups in terms of epidural fibrosis (p=0.164) and arachnoid involvement (p=0.303). Conclusion: Intraoperative rifamycin irrigation tends to reduce epidural fibrosis formation risk, although not statistically significant. [ABSTRACT FROM AUTHOR]

Abstract The controlled delivery of multiple drugs from biomaterials is a timely challenge. In particular the nanocomposite approach offers a unique opportunity to combine the scaffold-forming ability and biocompatibility of hydrogels with the versatile and tunable drug release properties of micro- or nano-carriers. Here, we show that collagen-silica nanocomposites allowing for the prolonged release of two topical antibiotics are promising medicated dressings to prevent infection in wounds. For this purpose, core–shell silica particles loaded with gentamicin sulfate and sodium rifamycin were combined with concentrated collagen type I hydrogels. A dense fibrillar network of collagen exhibiting its typical periodic banding pattern and a homogenous particle distribution were observed by scanning electron microscopy. Antibiotics release from nanocomposites allowed a sustained antibacterial effect against Staphylococcus aureus over 10 days in vitro. The acute dermal irritation test performed on albino rabbit skin showed no sign of severe inflammation. The antibacterial efficiency of nanocomposites was evaluated in vivo in a model of cutaneous infection, showing a 2 log steps decrease in bacterial population when loaded systems were used. In parallel, the histological examination indicated the absence of M1 inflammatory macrophages in the wound bed after treatment. Taken together, these results illustrate the potentialities of the nanocomposite approach to develop collagen-based biomaterials with controlled dual drug delivery to prevent infection and promote cutaneous wound repair. Highlights • Improved collagen hydrogels performance • Co-deliver two types of antibiotic molecules • In vivo antimicrobial activity • Confirmed nanocomposites biocompatibility [ABSTRACT FROM AUTHOR]

Thí nghiệm được thực hiện nhằm đánh giá khả năng lọc và hấp thụ dinh dưỡng của Artemia từ vi khuẩn trong điều kiện gnotobiotic (là điều kiện đã biết được loài vi khuẩn trong môi trường nuôi). Artemia được cho ăn với thức ăn pha trộn theo phần trăm giữa nấm men Saccharomyces cerevisiae dòng mnn9 và vi khuẩn HT3 (Tamlana sp. ZJU HZ22) đã được đánh dấu chất đồng vị bền N15, phần trăm của vi khuẩn trong khẩu phần ăn được tăng dần 25% theo nghiệm thức, và rifamycin được sử dụng với nồng độ 10 ppm để kiềm hãm sự phân chia của vi khuẩn (tránh làm giảm đi hàm lượng N15 trong vi khuẩn). Kết quả cho thấy rifamycin không ảnh hưởng đến tỉ lệ sống và tăng trưởng của Artemia sau 6 ngày nuôi. Hàm lượng N15 tích tụ trong mô của Artemia tỉ lệ thuận với sự tăng dần của vi khuẩn trong khẩu phần ăn. Kết quả này đã làm sáng tỏ Artemia có khả năng tiêu hóa và hấp thụ dinh dưỡng từ vi khuẩn và Artemia tiêu thụ nhiều vi khuẩn khi điều kiện nuôi thiếu thức ăn.